Portman DS et al. (2004) Mol Cell "Toward the computable transcriptome."

Bohmann D, Portman DS

[Mol Cell, 2004]

Applying a combination of innovative approaches to understanding neuronal gene regulation in C. elegans, an article in the latest Developmental Cell (Wenick and Hobert, 2004) gives hope that reading the genome''s transcriptional regulatory code may one day be possible.

Baylis HA (2005) Cell "VAV's got rhythm."

Baylis HA

[Cell, 2005]

Biological rhythms with periods of less than a day are physiologically important but poorly understood. In this issue of Cell, Norman, Maricq, and colleagues (Norman et al., 2005) show that VAV-1, a guanine nucleotide exchange factor for Rho-family GTPases, is necessary for three rhythmic behaviors in the nematode Caenorhabditis elegans: feeding, defecation, and ovulation.

Scharf A et al. (2021) Front Cell Dev Biol "Reproductive Aging in Caenorhabditis elegans: From Molecules to Ecology."

Pohl F, Egan BM, Kornfeld K, Scharf A, Kocsisova Z

[Front Cell Dev Biol, 2021]

Aging animals display a broad range of progressive degenerative changes, and one of the most fascinating is the decline of female reproductive function. In the model organism Caenorhabditis elegans, hermaphrodites reach a peak of progeny production on day 2 of adulthood and then display a rapid decline; progeny production typically ends by day 8 of adulthood. Since animals typically survive until day 15 of adulthood, there is a substantial post reproductive lifespan. Here we review the molecular and cellular changes that occur during reproductive aging, including reductions in stem cell number and activity, slowing meiotic progression, diminished Notch signaling, and deterioration of germ line and oocyte morphology. Several interventions have been identified that delay reproductive aging, including mutations, drugs and environmental factors such as temperature. The detailed description of reproductive aging coupled with interventions that delay this process have made C. elegans a leading model system to understand the mechanisms that drive reproductive aging. While reproductive aging has dramatic consequences for individual fertility, it also has consequences for the ecology of the population. Population dynamics are driven by birth and death, and reproductive aging is one important factor that influences birth rate. A variety of theories have been advanced to explain why reproductive aging occurs and how it has been sculpted during evolution. Here we summarize these theories and discuss the utility of C. elegans for testing mechanistic and evolutionary models of reproductive aging.

Komura T et al. (2012) Adv Exp Med Biol "Caenorhabditis elegans as an alternative model to study senescence of host defense and the prevention by immunonutrition."

Shibamura A, Ikeda T, Hoshino K, Komura T, Nishikawa Y

[Adv Exp Med Biol, 2012]

Whether nutritional control can retard senescence of immune function and decrease mortality from infectious diseases has not yet been established; the difficulty of establishing a model has made this a challenging topic to investigate. Caenorhabditis elegans has been extensively used as an experimental system for biological studies. Particularly for aging studies, the worm has the advantage of a short and reproducible life span. The organism has also been recognized as an alternative to mammalian models of infection with bacterial pathogens in this decade. Hence we have studied whether the worms could be a model host in the fields of immunosenescence and immunonutrition. Feeding nematodes lactic acid bacteria (LAB) resulted in increases in average life span of the nematodes compared to those fed Escherichia coli strain OP50, a standard food bacteria. The 7-day-old nematodes fed LAN from age 3 days were clearly endurable to subsequent salmonella infection compared with nematodes fed OP50 before the salmonella infection. The worm could be a unique model to study effects of food factors on longevity and host defense, so-called immunonutrition. Then we attempted to establish an immunosenescence model using C. elegans. We focused on the effects of worm age on the Legionella infection and the prevention by immunonutrition. No significant differences in survival were seen between 3-day-old worms fed OP50 and 3-day-old worms infected with virulent Legionella strains. However, when the worms were infected from 7.5 days after hatching, the virulent Legionella strains were obviously nematocidal for the worms' immunosenescence. In contrast, nematodes fed with bifidobacteria prior to Legionella infection were resistant to Legionella. C. elegans could act as a unique alternative host for immunosenescence and resultant opportunistic infection, and immunonutrition researches.

Hammond SM et al. (2002) Nature Reviews Genetics "Post-transcriptional gene silencing by double-stranded RNA."

Hammond SM, Caudy AA, Hannon GJ

[Nature Reviews Genetics, 2002]

Imagine being able to knock out your favourite gene with only a day's work. Not just in one model system, but in virtually any organism: plants, flies, mice or cultured cells. This sort of experimental dream might one day become reality as we learn to harness the power of RNA interference, the process by which double-stranded RNA induces the silencing of homologous endogenous genes. How this phenomenon works is slowly becoming clear, and might help us to develop an effortless tool to probe gene function in cells and animals.

Schierenberg E et al. (1992) Seminars in Developmental Biology "The establishment of embryonic axes and determination of cell fates in embryos of the nematode Caenorhabditis elegans."

Schierenberg E, Strome S

[Seminars in Developmental Biology, 1992]

At the 4-cell stage of the C. elegans embryo, three axes can be defined: anterior-posterior (A-P), dorsal-ventral (D-V), and left-right (L-R). The A-P axis first becomes obvious in the newly fertilized 1-cell embryo. Pronouned cytoplasmic assymmetries arise along the A-P axis during the first cell cycle, after which the zygote undergoes a series of stem cell-like cleavages with an A-P orientation of the mitotic spindle; these cleavages generate several somatic founder cells and a primordial germ cell. The D-V and L-R axes are defined by the direction of spindle rotation as the 2-cell embryo divides into four cells. In contrast to the A-P axis, there do not appear to be cellular asymmetries associated with the D-V and L-R axes, and both axes can easily be reversed by micromanipulation. Thus, with respect to the roles that the embryonic axes serve in cell-fate determination in the early C. elegans embryo, it appears that internally transmitted developmental information is differentially segregated along the A-P axis, but not along the D-V or L-R axes. Instead, D-V and L-R differences in the fates of cells within lineages appear to be dictated by differential

Sadeghian F et al. (2022) Life (Basel) "Functional Insights into Protein Kinase A (PKA) Signaling from C. elegans."

Castaneda PG, Sadeghian F, Cram EJ, Amin MR

[Life (Basel), 2022]

Protein kinase A (PKA), which regulates a diverse set of biological functions downstream of cyclic AMP (cAMP), is a tetramer consisting of two catalytic subunits (PKA-C) and two regulatory subunits (PKA-R). When cAMP binds the PKA-R subunits, the PKA-C subunits are released and interact with downstream effectors. In Caenorhabditis elegans (C. elegans), PKA-C and PKA-R are encoded by kin-1 and kin-2, respectively. This review focuses on the contributions of work in C. elegans to our understanding of the many roles of PKA, including contractility and oocyte maturation in the reproductive system, lipid metabolism, physiology, mitochondrial function and lifespan, and a wide variety of behaviors. C. elegans provides a powerful genetic platform for understanding how this kinase can regulate an astounding variety of physiological responses.

Riddle DL (1987) Int J Parasitol "Post-embryonic development in Caenorhabditis elegans."

Riddle DL

[Int J Parasitol, 1987]

The free-living soil nematode, Caeorhabditis elegans, is an animal well-suited for developmental studies owing to its genetic and anatomical simplicity. The structure and life cycle of this one-millimeter-long roundworm make it a particularly attractive laboratory model for the analysis of cell lineage, gene action, morphogenesis and behavior during post-embryonic development. Furthermore, similarities between this nematode and other species that are parasites of plants or animals make it a potentially powerful model for understanding the genetic and physiological basis of parasite development and survival strategies. Both normal and mutant strains of C. elegans can be grown rapidly (3-day life cycle) and in large quantity in the laboratory on bacteria (Escherichia coli) as the food source. This is important for biochemical analyses, and for detection of the rare mutants or genetic recombinants that are often extremely useful in genetic

Emmons SW (2015) Philos Trans R Soc Lond B Biol Sci "The beginning of connectomics: a commentary on White et al. (1986) 'The structure of the nervous system of the nematode Caenorhabditis elegans'."

Emmons SW

[Philos Trans R Soc Lond B Biol Sci, 2015]

The article 'Structure of the nervous system of the nematode Caenorhabditis elegans' (aka 'The mind of a worm') by White et al., published for the first time the complete set of synaptic connections in the nervous system of an animal. The work was carried out as part of a programme to begin to understand how genes determine the structure of a nervous system and how a nervous system creates behaviour. It became a major stimulus to the field of C. elegans research, which has since contributed insights into all areas of biology. Twenty-six years elapsed before developments, notably more powerful computers, made new studies of this kind possible. It is hoped that one day knowledge of synaptic structure, the connectome, together with results of many other investigations, will lead to an understanding of the human brain. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

Giacomotto J et al. (2010) Br J Pharmacol "High-throughput screening and small animal models, where are we?"

Segalat L, Giacomotto J

[Br J Pharmacol, 2010]

Current high-throughput screening methods for drug discovery rely on the existence of targets. Moreover, most of the hits generated during screenings turn out to be invalid after further testing in animal models. To by-pass these limitations, efforts are now being made to screen chemical libraries on whole animals. One of the most commonly used animal model in biology is the murine model Mus musculus. However, its cost limit its use in large-scale therapeutic screening. In contrast, the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the fish Danio rerio are gaining momentum as screening tools. These organisms combine genetic amenability, low cost and culture conditions that are compatible with large-scale screens. Their main advantage is to allow high-throughput screening in a whole-animal context. Moreover, their use is not dependent on the prior identification of a target and permits the selection of compounds with an improved safety profile. This review surveys the versatility of these animal models for drug discovery and discuss the options available at this day.